Abstract: Studies on the total synthesis and evaluation of anti-tumor antibiotics including bleomycin A/2, phomazarin, roseophilin, ningalin A. lamellarin O, lukianol A, storniamide A, anhydrolycorinone, hippadine, anhydrolycorinium chloride, rebeccamycin, (20S)-camptothecin, vindoline (vincristine/vinblastine), rubrolone, and key structural analogs are detailed. In the course of these studies, the investigation, development, and implementation of: (1) heteroaromatic azadiene Diels-Alder reactions, (2) the LUMO/diene-controlled Diels-Alder reactions of N-sulfonyl-l-aza- 1,3-butadienes, (3) the intramolecular Diels-Alder reactions of O-methyl alpha, beta-unsaturated oximes, (4) the thermal reactions of cyclopropenone ketals including those of reversibly generated pi- delocalized singlet vinylcarbenes, (5) tandem Diels-Alder/1,3-dipolar cycloadditions of 1,3,4-oxadiazoles, and (6) acyl radical alkene addition reactions will be pursued and provide the opportunity to comprehensively extend past studies. An additional application of the synthetic methodology to the preparation of pyridoxol is described. The proposed studies include the examination of anti-tumor antibiotics that mediate their cellular effects through sequence selective DNA binding and provide well-defined problems on the design, preparation, and evaluation of synthetic, mechanism-based anti-tumor agents in which fundamental studies of their structural features responsible for DNA binding affinity, selectivity, and functional reactivity may be addressed.